The present invention relates to new peptide compounds, a process for the preparation thereof and pharmaceutical compositions containing them. The compounds of the present invention have a valuable pharmacological use as platelet anti-aggregation agents.
It is known that the prevention of thrombosis and atherosclerosis is dependent on the control and regulation of platelet aggregation. The formation of a thrombus or blood clot is linked with the presence of fibrinogen which, as a result of its interaction with a specific receptor, causing cell adhesion, participates in platelet aggregation. The mechanism is general for all inducers and it is therefore particularly valuable to seek to regulate or inhibit fibrinogen-dependent aggregation.
Peptide compounds possessing anti-aggregation properties are already known. There may be mentioned by way of example:
patent EP-A-319506 where the following peptide chain is found: EQU --Arg--Gly--Asp--O-methyltyrosineamide PA1 patent U.S. Pat. No. 4,578,079 which describes peptides having the formula: EQU --Arg--Gly--Asp--Thr--, EQU --Arg--Gly--Asp--Cys-- EQU or EQU --Arg--Gly--Asp--Ser-- PA1 and PA1 patent EP-A-220957 disclosing peptides having the formula: EQU --Lys--Arg--Gly--Asp-- EQU or EQU --Arg--Arg--Gly--Asp--. PA1 A represents an arginine (Arg) or lysine (Lys) residue, PA1 R.sub.1 represents a linear, branched or cyclic amino acid residue, the amine grouping of which is not in the .alpha.-position relative to the carbonyl grouping, and PA1 R.sub.2 is chosen among --NH.sub.2 and --OH, PA1 1) deprotection of the substrate by means of a suitable base, such as, for example, piperidine, PA1 2) coupling of a protected amino acid in the presence of a coupling reagent customarily used in peptide synthesis, such as, for example, the pair DCC/HOBT, TBTU/DIEA, BOP/DIEA or DPPA, PA1 R.sub.1 and A are as defined above, PA1 R represents the resin support, PA1 P.sub.1 is a protecting grouping, such as, for example, Fmoc or Boc, PA1 P.sub.2 is an aspartic acid protecting grouping, such as, for example, OtBu or Bzl, PA1 P.sub.3 is a protecting grouping, for example Pmc in the case of arginine or Boc in the case of lysine,
Patents EP-A-275748 and EP-A-341915 propose tetrapeptides having the formula X.sub.1 --Arg--Gly--Asp--Trp--X.sub.2 in which X.sub.1 and X.sub.2 may be residues of natural amino acids.